TY  - JOUR
AU  - Oeckl, Patrick
AU  - Mayer, Benjamin
AU  - Bateman, Randall J
AU  - Day, Gregory S
AU  - Fox, Nick C
AU  - Huey, Edward D
AU  - Ibanez, Laura
AU  - Ikeuchi, Takeshi
AU  - Jucker, Mathias
AU  - Lee, Jae-Hong
AU  - Levin, Johannes
AU  - Llibre-Guerra, Jorge J
AU  - Lopera, Francisco
AU  - McDade, Eric
AU  - Morris, John C
AU  - Niimi, Yoshiki
AU  - Roh, Jee Hoon
AU  - Sánchez-Valle, Raquel
AU  - Schofield, Peter R
AU  - Otto, Markus
TI  - Early increase of the synaptic blood marker β-synuclein in asymptomatic autosomal dominant Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 21
IS  - 4
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-00510
SP  - e70146
PY  - 2025
AB  - β-synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear.We investigated serum β-synuclein in 69 cognitively unimpaired mutation non-carriers, 78 cognitively unimpaired AD mutation carriers (asymptomatic AD), and 31 symptomatic mutation carriers from the Dominantly Inherited Alzheimer Network.β-synuclein levels were already higher in asymptomatic AD mutation carriers compared to non-carriers and highest in symptomatic carriers. Longitudinal trajectories and correlation analyses indicated that β-synuclein levels start to rise after amyloid deposition preceding axonal degeneration, brain atrophy and hypometabolism, and cognitive decline. β-synuclein levels were associated with cognitive impairment and gradually increased with declining cognition.Our study supports the use of blood β-synuclein to track synaptic changes in preclinical AD and as a surrogate marker for cognitive impairment which might be used in early diagnosis and to support patient selection and monitoring of treatment effects in clinical trials.Blood β-synuclein levels were already higher in asymptomatic Alzheimer's disease (AD) mutation carriers. Blood β-synuclein levels were highest in symptomatic AD mutation carriers. Blood β-synuclein levels start to rise 11 years before symptom onset. Rise of β-synuclein precedes axonal degeneration, brain atrophy, and cognitive decline. β-synuclein levels gradually increased with declining cognition.
KW  - Humans
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: pathology
KW  - Male
KW  - Female
KW  - Biomarkers: blood
KW  - Middle Aged
KW  - Mutation: genetics
KW  - beta-Synuclein: blood
KW  - Aged
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - Synapses
KW  - Cognitive Dysfunction: blood
KW  - Longitudinal Studies
KW  - asymptomatic mutation carriers (Other)
KW  - autosomal dominant Alzheimer´s disease (Other)
KW  - blood biomarker (Other)
KW  - preclinical Alzheimer´s disease (Other)
KW  - synaptic degeneration (Other)
KW  - β‐synuclein (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - beta-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40207431
DO  - DOI:10.1002/alz.70146
UR  - https://pub.dzne.de/record/277978
ER  -